Article
Chemistry, Medicinal
Wenzhong Yan, Lijun Ling, Yiran Wu, Kexin Yang, Ruiquan Liu, Jinfeng Zhang, Simeng Zhao, Guisheng Zhong, Suwen Zhao, Hualiang Jiang, Chengying Xie, Jianjun Cheng
Summary: Adenosine serves as an immunosuppressive factor in the tumor microenvironment by activating the A(2A) adenosine receptor. Dual-acting compounds targeting A(2A)R and HDAC are potentially effective immunotherapeutic agents that show promising antitumor activity in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ying-Chao Duan, Lin-Feng Jin, Hong-Mei Ren, Shao-Jie Zhang, Yue-Jiao Liu, Yong-Tao Xu, Zi-Hao He, Yu Song, Hang Yuan, Shu-Hui Chen, Yuan-Yuan Guan
Summary: LSD1 and HDAC are closely related in various human cancers, and simultaneous pharmacological inhibition of them can have synergistic anti-cancer effects. Novel LSD1/HDAC bifunctional inhibitors were designed and synthesized, with compounds 5d and 5m showing potent anti-cancer activities and selectivity against other enzymes. Compound 5m, in particular, demonstrated superior in vitro anticancer potency against gastric cancer cell lines compared to existing drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Anqi Li, Wenwen Zheng, Boren Xiao, Wenjun Huang, Lulu Li, Minglang Luo, Zijian Liu, Bizhu Chu, Yuyang Jiang
Summary: In this study, a series of novel dual JMJD3 and HDAC inhibitors were designed and synthesized using rational drug design strategy. Compound A5b exhibited potent inhibitory activity against JMJD3 and HDAC1/6, and showed favorable cytotoxicity against human cancer cells. Mechanistic studies revealed that A5b increased histone modification, inhibited cancer cell abilities, induced apoptosis and cell cycle arrest. These findings suggest that A5b can be a potential compound for cancer therapy as the first dual inhibitor against JMJD3 and HDAC.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Pharmacology & Pharmacy
Lucile Hoch, Nathalie Bourg, Fanny Degrugillier, Celine Bruge, Manon Benabides, Emilie Pellier, Johana Tournois, Gurvan Mahe, Nicolas Maignan, Jack Dawe, Maxime Georges, David Papazian, Nik Subramanian, Stephanie Simon, Pascale Fanen, Cedric Delevoye, Isabelle Richard, Xavier Nissan
Summary: This study investigates the protein degradation defect in LGMD R3 and identifies the HDAC inhibitor givinostat as a potential therapeutic option. The findings provide new treatment strategies for LGMD R3 patients and offer insights for the treatment of other genetic diseases with similar protein degradation defects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yunpeng Zhao, Zefu Yao, Wandi Ren, Xinying Yang, Xuben Hou, Shengda Cao, Hao Fang
Summary: In this study, a series of 8-substituted quinoline-2-carboxamide derivatives were synthesized as potent HDAC inhibitors. Compound 21g showed the most potent inhibitory activity and low toxicity against normal cells, making it a potential lead compound for further development.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Marie Kuehne, Henry Lindemann, Christian Grune, Daniel Schroeder, Zoltan Cseresnyes, Maren Godmann, Andreas Koschella, Marc Thilo Figge, Christian Eggeling, Dagmar Fischer, Thomas Heinze, Thorsten Heinzel
Summary: Bio-based nanoparticles (NPs) as drug carriers have rapid cellular uptake, no cytotoxicity, and ability to induce histone H3 hyperacetylation, making them suitable for treating inflammation, sepsis, and cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Medicinal
Negar Omidkhah, Razieh Ghodsi
Summary: NO-HDAC dual inhibitors have demonstrated satisfactory therapeutic effects in various diseases and possess high therapeutic potential.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jingjing Deng, Baogeng Hou, Xiaohan Hou, Yuxin Chen, Tao Zhang, Hua Chen, Yuanze Wang, Xiaoyang Li
Summary: In this study, a series of benzamide-based PI3K/HDAC dual inhibitors were designed and synthesized, and representative compound PH14 showed potent inhibitory activity toward PI3K alpha and HDAC3, as well as the ability to promote apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jie Wang, Zhuoxian Cao, Fang Wang, Pan Wang, Jianxiong An, Xiaozhong Fu, Ting Liu, Yan Li, Yongjun Li, Yonglong Zhao, Hening Lin, Bin He
Summary: The study discusses the rational design, synthesis, biological evaluation, molecular docking, and in vivo efficacy study of a class of HDAC inhibitors using N-acetyl lysine mimics derived from cysteine. These inhibitors demonstrated potent HDAC inhibition and broad cytotoxicity against several cancer cell lines, and compound 13d showed significant tumor growth inhibition in a A549 xenograft mice model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Suhua Wang, Siyuan Han, Weiyan Cheng, Ruoyang Miao, Shasha Li, Xin Tian, Quancheng Kan
Summary: This study suggests that incorporating HDAC pharmacophores into the CDK4 inhibitor scaffold to design CDK/HDAC inhibitors may enhance the anti-tumor potency of the compounds.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Pharmacology & Pharmacy
Xiaopan Gao, Bo Qin, Pu Chen, Kaixiang Zhu, Pengjiao Hou, Justyna Aleksandra Wojdyla, Meitian Wang, Sheng Cui
Summary: This study provided structural frameworks for PLpro inhibitor design targeting SARS-CoV-2, showing that existing SARS-CoV PLpro inhibitors have some efficacy against SARS-CoV-2 and explored the inhibition mechanism of GRL0617.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Biochemistry & Molecular Biology
Ligong Liu, Lilong Dong, Erika Bourguet, David P. Fairlie
Summary: This review summarizes the phenotypes of individual class IIa HDAC proteins and compounds targeting their enzymatic catalytic domain, focusing on their effects in gene regulation and disease. Silencing selected class IIa HDACs or their enzymatic properties can have beneficial or detrimental effects. Targeting the CD of class IIa HDACs may lead to more selective therapeutic agents with fewer side-effects.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jiayuan Liu, Xianglei Zhang, Guofeng Chen, Qiang Shao, Yi Zou, Zhewen Li, Haixia Su, Minjun Li, Yechun Xu
Summary: This study discovered novel drug-like PDE4 inhibitors through high-throughput drug repurposing screening and elucidated their molecular mechanisms of action through crystal structure analysis. It also revealed that CVT-313 is a potent PDE5 inhibitor and led to the discovery of a new inhibitor with improved activity and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Eric R. Samuels, Irina F. Sevrioukova
Summary: The study identified an optimal head-group spacer length for improving the thermostability and inhibitory effect of CYP3A4, with the lead compound 3h showing the strongest binding and inhibition. The results suggest that a one-atom linker elongation was beneficial, while a two-atom linker extension led to decreased binding and inhibitory strength. The approach used in this study has resulted in the development of structurally simpler inhibitors that are superior to ritonavir.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Jingru Yang, Cong Song, Xianquan Zhan
Summary: Protein acetylation is an important molecular event that is involved in various biological processes, including carcinogenesis. The modulation of protein acetylation levels can lead to the discovery of therapeutic drugs and lay the foundation for precision medicine in oncology.
FRONTIERS IN ENDOCRINOLOGY
(2022)